Inflammation and oxidative stress are key mediators in AKB48-induced neurotoxicity in vitro

Öztaş, Ezgi; Asadi, Mahmoud; Çeliksöz, Müzeyyen; Özhan, Gül

doi:10.1016/j.tiv.2018.12.005

Cited by 22 publications

(11 citation statements)

References 36 publications

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“…49 In the present study the IL-6 and TNF-α levels were increased with increasing the dose. The obtained data of the current study are in the same line with that obtained by Oztas et al, 50 who reported the impact of the synthetic cannabinoid AKB48 in the induction of a dose dependent significant increment in TNF-α and IL-6, revealing the neurotoxicity of AKB48 which is one of the third-generation psychoactive synthetic cannabinoid (Apinca). The obtained data in the current study also confirmed the finding of Guler et al 51 who recorded a significant elevation of IL-6, and TNF-α serum levels in synthetic cannabinoids users.…”

Section: Discussionsupporting

confidence: 92%

“…It has been reported that SCs often act by modulating the action of endo-cannabinoids on CB1 50, 72, 73 and CB2 receptors 74,75 to exert their effects as a result of synthetic cannabinoids administration. Oztas et al, 50 reported that cannabinoid B1receptor expression was well markedly increased under the influence of synthetic cannabinoid AKB48 administration in a dose dependent manner, meanwhile cannabinoid CB2 receptor was not expressed in SH-SY5Y cells. On the other hand our data recorded a significant decline in the mRNA expression of the both examined receptors under the influence of AMB-FUBINACA administration at the three examined doses.…”

Section: Discussionmentioning

confidence: 99%

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Oxidative Stress, Inflammation and Apoptosis are the Main Mediators in AMB-FUBINACA Induced Brain Injury in Male Albino Rats

Esawy

Eltablawy

El-Fattah

et al. 2021

Azhar International Journal of Pharmaceutical and Medical Scien

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Synthetic cannabinoids (SCs) abuse is a serious social problem worldwide. It can cause severe toxicity, including seizures and even death. This study aims to examine the role of sub-chronic administration of AMB-FUBINACA SC in the induction of brain injury. 32 Male adult rats divided into four groups (8 rats per cage) were used, Control group: Intraperitoneally (IP) injected with 0.5 ml of the vehicle, and the others each one of them IP injected with 0.5 ml of the three different doses of AMB-FUBINACA as following: Group1: 1mg/kg, Group 2: 3mg/kg and Group 3: 4mg/kg. The drug was injected once a day for six consecutive days. Tremors were observed 30 minutes following drug injection especially with 3 and 4 mg/kg examined doses followed by depressant effect. Then rats became hyperactive and aggressive. The drug administration induced a significant disturbance in the redox status of brain and significantly increased tumor necrosis factor-α (TNF-α), interlukin-6 (IL-6) and the soluble calcium binding protein B (S100B) serum levels. In addition, the mRNA expression levels of nuclear factor kappa B (NF-𝜅B), mitogen activated protein kinase p38 (MAPK p38) and Caspase-3 were significantly up-regulated. Meanwhile, the mRNA expression levels of Cannabinoid receptors (CB1R, CB2R) and brain derived neurotrophic factor (BDNF) were significantly downregulated. The obtained results demonstrated that, AMB-FUBINACA harmful effects increase with the dose, which was supported by the brain histopathological examination. We concluded that, AMB-FUBINACA has a functional and structural deleterious central nervous system (CNS) effects with sub chronic exposure in adult male rats. The induced brain injury and seizures that accompanied with the synthetic cannabinoids abuse might be mediated through the generation of oxidative stress, activating inflammatory cellular signaling mechanism and neural cell death via apoptosis.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Oxidative Stress, Inflammation and Apoptosis are the Main Mediators in AMB-FUBINACA Induced Brain Injury in Male Albino Rats

Esawy

Eltablawy

El-Fattah

et al. 2021

Azhar International Journal of Pharmaceutical and Medical Scien

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“…The primer sequences and the annealing temperatures of the genes are provided in Table 1. Additionally, the mRNA expression levels of IRE1‐α, GADD153 , and GRP78 were determined by using LightCycler 480 Probes Master Mix and Catalog Assays with 50 ng cDNA in the final mix as previously described by Oztas et al [ 28 ] The cycle threshold ( C t ) of the apoptosis‐related genes and β‐actin, a housekeeping gene, was determined, and the control value was taken as 1 and other values were evaluated as a percentage increase or decrease.…”

Section: Methodsmentioning

confidence: 99%

Zoledronic acid‐induced oxidative damage and endoplasmic reticulum stress‐mediated apoptosis in human embryonic kidney (HEK‐293) cells

Kara

Boran

Öztaş

et al. 2022

J Biochem & Molecular Tox

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Zoledronic acid, a nitrogen‐containing bisphosphonate drug, is used for the treatment of osteoporosis, Paget's disease of bone, and tumor‐induced osteolysis. Zoledronic acid has also gained a place in cancer treatment due to its cytotoxic and antiproliferative effects in many cancer cells. Although zoledronic acid is considered safe, kidney damage is still one of the concerns in therapeutic doses. In the study, the aim was to assess the nephrotoxic profiles of zoledronic acid in the human embryonic kidney (HEK‐293) cells. Cytotoxicity evaluation was performed by 3‐[4,5‐dimethylthiazol‐2‐yl]−2,5‐diphenyl‐tetrazolium bromide (MTT) and neutral red uptake tests, while oxidative stress was performed by reactive oxygen species (ROS) production via flow cytometry, and the incomprehensible evaluation of ROS‐related genes by RT‐PCR and apoptosis was performed with Annexin‐PI analysis in flow cytometry. The obtained result showed that zoledronic acid inhibited cell viability (IC50 values were determined as 273.16  by MTT) and cell proliferation in a concentration‐dependent manner, induced ROS production, caused glutathione depletion, and increased oxidative stress index and endoplasmic reticulum (ER) stress, indicating severe cellular stress. The expression levels of oxidative damage (L‐fabp, α‐GST, Nrf2, and HMOX1), ER stress (CASP4, IRE1‐α, GADD153, and GRP78), and apoptosis (Bcl‐2, Bax, Cyt‐c, p53, CASP9, CASP3, NF‐κB, TNF‐α, and JNK) related genes were altered as well as IRE1‐α protein levels. Herein, we were the first to show that increased oxidative stress and ER stress resulting in apoptosis are the key molecular pathways in zoledronic acid‐induced nephrotoxicity equivalent to clinically administered concentrations.

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“…Activation of mitogen-activated protein kinase 8 (MAPK8) is necessary for inflammation and oxidative stress responses in human bone marrow neuroblastoma. 27 In the current study, we discovered that MAPK8 serves as a direct target of miR-873-5p. Therefore, we hypothesized that UCA1-dependent endothelial cell injuries induced by ox-LDL might be mediated by the miR-873-5p/MAPK8 axis.…”

Section: Discussionmentioning

confidence: 63%

“…Here, we demonstrated that UCA1 directly binds to miR‐873‐5p, thereby suppressing its expression in endothelial cells. Activation of mitogen‐activated protein kinase 8 (MAPK8) is necessary for inflammation and oxidative stress responses in human bone marrow neuroblastoma 27 . In the current study, we discovered that MAPK8 serves as a direct target of miR‐873‐5p.…”

Section: Discussionmentioning

confidence: 84%

Silencing of UCA1 attenuates the ox‐LDL‐induced injury of human umbilical vein endothelial cells via miR‐873‐5p/MAPK8 axis

Zhang

2022

The Kaohsiung J of Med Scie

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LncRNA UCA1 plays a vital role in cardiovascular diseases. Endothelial cell dysfunction is a prerequisite for atherosclerosis (AS) development. However, the pathophysiological role of UCA1 in endothelial cell dysfunction induced by ox‐LDL remains obscure. Here, we observed that UCA1 was upregulated in the sera of patients with AS and ox‐LDL‐treated endothelial cells. UCA1 knockdown dramatically reduced the cell apoptosis induced by ox‐LDL and the production of pro‐inflammatory cytokines and ROS in endothelial cells. Mechanistically, we found that UCA1 directly targeted miR‐873‐5p. UCA1 knockdown increased, while UCA1 overexpression decreased the expression of miR‐873‐5p. Further, we found that mitogen‐activated protein kinase 8 (MAPK8) was a downstream target gene of miR‐873‐5p. MAPK8 overexpression or miR‐873‐5p knockdown reduced the enhancement of ox‐LDL‐induced cell apoptosis, oxidative stress, and pro‐inflammatory cytokine production conferred by UCA1 knockdown. In conclusion, UCA1 can protect Human Umbilical Vein Endothelial Cells from ox‐LDL‐induced injury via the miR‐873‐5p/MAPK8 axis.

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Inflammation and oxidative stress are key mediators in AKB48-induced neurotoxicity in vitro

Cited by 22 publications

References 36 publications

Oxidative Stress, Inflammation and Apoptosis are the Main Mediators in AMB-FUBINACA Induced Brain Injury in Male Albino Rats

Oxidative Stress, Inflammation and Apoptosis are the Main Mediators in AMB-FUBINACA Induced Brain Injury in Male Albino Rats

Zoledronic acid‐induced oxidative damage and endoplasmic reticulum stress‐mediated apoptosis in human embryonic kidney (HEK‐293) cells

Silencing of UCA1 attenuates the ox‐LDL‐induced injury of human umbilical vein endothelial cells via miR‐873‐5p/MAPK8 axis

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